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Seminars in Respiratory and Critical... Dec 2019Although survival of individuals with cystic fibrosis (CF) has been continuously improving for the past 40 years, respiratory failure secondary to recurrent pulmonary... (Review)
Review
Although survival of individuals with cystic fibrosis (CF) has been continuously improving for the past 40 years, respiratory failure secondary to recurrent pulmonary infections remains the leading cause of mortality in this patient population. Certain pathogens such as , methicillin-resistant , and species of the complex continue to be associated with poorer clinical outcomes including accelerated lung function decline and increased mortality. In addition, other organisms such as anaerobes, viruses, and fungi are increasingly recognized as potential contributors to disease progression. Culture-independent molecular methods are also being used for diagnostic purposes and to examine the interaction of microorganisms in the CF airway. Given the importance of CF airway infections, ongoing initiatives to promote understanding of the epidemiology, clinical course, and treatment options for these infections are needed.
Topics: Bacterial Infections; Burkholderiaceae; Cystic Fibrosis; Humans; Methicillin-Resistant Staphylococcus aureus; Microbiota; Mycoses; Pseudomonas aeruginosa; Respiratory Tract Infections; Virus Diseases
PubMed: 31887768
DOI: 10.1055/s-0039-1698464 -
Drug Resistance Updates : Reviews and... Sep 2016The genus Burkholderia comprises metabolically diverse and adaptable Gram-negative bacteria, which thrive in often adversarial environments. A few members of the genus... (Review)
Review
The genus Burkholderia comprises metabolically diverse and adaptable Gram-negative bacteria, which thrive in often adversarial environments. A few members of the genus are prominent opportunistic pathogens. These include Burkholderia mallei and Burkholderia pseudomallei of the B. pseudomallei complex, which cause glanders and melioidosis, respectively. Burkholderia cenocepacia, Burkholderia multivorans, and Burkholderia vietnamiensis belong to the Burkholderia cepacia complex and affect mostly cystic fibrosis patients. Infections caused by these bacteria are difficult to treat because of significant antibiotic resistance. The first line of defense against antimicrobials in Burkholderia species is the outer membrane penetration barrier. Most Burkholderia contain a modified lipopolysaccharide that causes intrinsic polymyxin resistance. Contributing to reduced drug penetration are restrictive porin proteins. Efflux pumps of the resistance nodulation cell division family are major players in Burkholderia multidrug resistance. Third and fourth generation β-lactam antibiotics are seminal for treatment of Burkholderia infections, but therapeutic efficacy is compromised by expression of several β-lactamases and ceftazidime target mutations. Altered DNA gyrase and dihydrofolate reductase targets cause fluoroquinolone and trimethoprim resistance, respectively. Although antibiotic resistance hampers therapy of Burkholderia infections, the characterization of resistance mechanisms lags behind other non-enteric Gram-negative pathogens, especially ESKAPE bacteria such as Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa.
Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; Burkholderia; Burkholderia Infections; Burkholderia mallei; Burkholderia pseudomallei; DNA Gyrase; Drug Resistance, Multiple, Bacterial; Gene Expression Regulation, Bacterial; Genes, MDR; Glanders; Horses; Humans; Melioidosis; Porins; Tetrahydrofolate Dehydrogenase
PubMed: 27620956
DOI: 10.1016/j.drup.2016.07.003 -
Trends in Microbiology Jan 2024is a Gram negative, facultative intracellular bacterium that resides in the rhizosphere of tropical soils. causes melioidosis, which is transmitted by cutaneous entry,...
is a Gram negative, facultative intracellular bacterium that resides in the rhizosphere of tropical soils. causes melioidosis, which is transmitted by cutaneous entry, ingestion, or inhalation of contaminated soil or water. Infection with can cause a wide array of clinical symptoms such as pneumonia, bone, joint, skin, genitourinary, and central nervous system infections, as well as parotid abscesses in children. Mammalian virulence is linked to the intracellular life cycle, which begins with attachment and internalization by host cells. can infect a wide range of eukaryotic cells, including macrophages, monocytes, and neutrophils, as well as nonphagocytic cells. Once internalized, a type 3 secretion system (T3SS) facilitates escape from the phagosome, and the bacteria replicate in the cytoplasm. Autotransporter protein BimA mediates actin polymerization, enabling to spread, cell to cell, using actin-based motility. This process, coupled with the activity of a type 6 secretion system (T6SS-5), results in host membrane fusion and the formation of multinucleated giant cells. Capsule polysaccharides also contribute to virulence and evasion of host innate immunity. Treatment of infections is complicated by the organism’s intrinsic resistance to multiple classes of antimicrobials, largely due to an abundance of efflux pumps and reduced outer membrane permeability. While is commonly associated with endemic ‘hotspots’ in southeast Asia and northern Australia, there is increasing evidence that it is likely endemic in a large range of tropical and subtropical areas, including regions in Africa, South America, the Middle East, Central America, and the Caribbean. Soil and climate conditions favorable for survival are also found in additional areas worldwide. Consequently, it is important for clinical and public health laboratories located outside of high-endemicity areas to be aware of , as well as for improved diagnostic and reporting methods.
Topics: Burkholderia pseudomallei; Burkholderia
PubMed: 37634974
DOI: 10.1016/j.tim.2023.07.008 -
Applied and Environmental Microbiology Mar 2021Mucoromycota representatives are known to harbor two types of endohyphal bacteria (EHB)--related endobacteria (BRE) and -related endobacteria (MRE). While both BRE and...
Mucoromycota representatives are known to harbor two types of endohyphal bacteria (EHB)--related endobacteria (BRE) and -related endobacteria (MRE). While both BRE and MRE occur in fungi representing all subphyla of Mucoromycota, their distribution is not well studied. Therefore, it is difficult to resolve the evolutionary history of these associations in favor of one of the following two alternative hypotheses explaining their origin: "early invasion" and "late invasion." Our main goal was to fill this knowledge gap by surveying Mucoromycota fungi for the presence of EHB. We screened 196 fungal strains from 16 genera using a PCR-based approach to detect bacterial 16S rRNA genes, complemented with fluorescence hybridization (FISH) imaging to confirm the presence of bacteria within the hyphae. We detected in ca. 20% of fungal strains. Some of these bacteria clustered phylogenetically with previously described BRE clades, whereas others grouped with free-living Importantly, the latter were detected in Umbelopsidales, which previously were not known to harbor endobacteria. Our results suggest that this group of EHB is recruited from the environment, supporting the late invasion scenario. This pattern complements the early invasion scenario apparent in the BRE clade of EHB. Bacteria living within fungal hyphae present an example of one of the most intimate relationships between fungi and bacteria. Even though there are several well-described examples of such partnerships, their prevalence within the fungal kingdom remains unknown. Our study focused on early divergent terrestrial fungi in the phylum Mucoromycota. We found that ca. 20% of the strains tested harbored bacteria from the family Not only did we confirm the presence of bacteria from previously described endosymbiont clades, we also identified a new group of endohyphal representing the genus We established that more than half of the screened strains were positive for bacteria from this new group. We also determined that, while previously described BRE codiverged with their fungal hosts, symbionts did not.
Topics: Burkholderiaceae; Fungi; Hyphae; In Situ Hybridization, Fluorescence; Polymerase Chain Reaction; RNA, Bacterial; RNA, Ribosomal, 16S
PubMed: 33483310
DOI: 10.1128/AEM.02707-20 -
Pathogens and Disease Aug 2016The Gram-negative proteobacteria genus Burkholderia encompasses multiple bacterial species that are pathogenic to humans and other vertebrates. Two pathogenic species of... (Review)
Review
The Gram-negative proteobacteria genus Burkholderia encompasses multiple bacterial species that are pathogenic to humans and other vertebrates. Two pathogenic species of interest within this genus are Burkholderia pseudomallei (Bpm) and the B. cepacia complex (Bcc); the former is the causative agent of melioidosis in humans and other mammals, and the latter is associated with pneumonia in immunocompromised patients. One understudied and shared characteristic of these two pathogenic groups is their ability to persist and establish chronic infection within the host. In this review, we will explore the depth of knowledge about chronic infections caused by persistent Bpm and Bcc. We examine the host risk factors and immune responses associated with more severe chronic infections. We also discuss host adaptation and phenotypes associated with persistent Burkholderia species. Lastly, we survey how other intracellular bacteria associated with chronic infections are combatted and explore possible future applications to target Burkholderia Our goal is to highlight understudied areas that should be addressed for a more thorough understanding of chronic Burkholderia infections and how to combat them.
Topics: Adaptation, Biological; Animals; Burkholderia; Burkholderia Infections; Chronic Disease; Host-Pathogen Interactions; Humans; Immune System; Melioidosis; Virulence Factors
PubMed: 27440810
DOI: 10.1093/femspd/ftw070 -
Viruses Jul 2021The increasing prevalence and worldwide distribution of multidrug-resistant bacterial pathogens is an imminent danger to public health and threatens virtually all... (Review)
Review
The increasing prevalence and worldwide distribution of multidrug-resistant bacterial pathogens is an imminent danger to public health and threatens virtually all aspects of modern medicine. Particularly concerning, yet insufficiently addressed, are the members of the complex (Bcc), a group of at least twenty opportunistic, hospital-transmitted, and notoriously drug-resistant species, which infect and cause morbidity in patients who are immunocompromised and those afflicted with chronic illnesses, including cystic fibrosis (CF) and chronic granulomatous disease (CGD). One potential solution to the antimicrobial resistance crisis is phage therapy-the use of phages for the treatment of bacterial infections. Although phage therapy has a long and somewhat checkered history, an impressive volume of modern research has been amassed in the past decades to show that when applied through specific, scientifically supported treatment strategies, phage therapy is highly efficacious and is a promising avenue against drug-resistant and difficult-to-treat pathogens, such as the Bcc. In this review, we discuss the clinical significance of the Bcc, the advantages of phage therapy, and the theoretical and clinical advancements made in phage therapy in general over the past decades, and apply these concepts specifically to the nascent, but growing and rapidly developing, field of Bcc phage therapy.
Topics: Bacteriophages; Burkholderia cepacia complex; Humans; Phage Therapy
PubMed: 34372537
DOI: 10.3390/v13071331 -
Current Opinion in Microbiology Feb 2016The Burkholderia genus contains a group of soil-dwelling Gram-negative organisms that are prevalent in warm and humid climates. Two species in particular are able to... (Review)
Review
The Burkholderia genus contains a group of soil-dwelling Gram-negative organisms that are prevalent in warm and humid climates. Two species in particular are able to cause disease in animals, B. mallei primarily infects Equus spp. and B. pseudomallei (BPS), that is able to cause potentially life-threatening disease in humans. BPS is naturally resistant to many antibiotics and there is no vaccine available. Although not a specialised human pathogen, BPS possesses a large genome and many virulence traits that allow it to adapt and survive very successfully in the human host. Key to this survival is the ability of BPS to replicate intracellularly. In this review we highlight recent advances in our understanding of the intracellular survival of BPS, including how it overcomes host immune defenses and other challenges to establish its niche and then spread the infection. Knowledge of these mechanisms increases our capacity for therapeutic interventions against a well-armed foe.
Topics: Actins; Animals; Burkholderia pseudomallei; Cytoplasm; DNA Replication; Giant Cells; Host-Pathogen Interactions; Humans; Melioidosis; Type VI Secretion Systems; Virulence; Virulence Factors
PubMed: 26803404
DOI: 10.1016/j.mib.2015.11.007 -
Expert Opinion on Biological Therapy Dec 2019: Two important pathogenic species within the genus , namely () and (), are the causative agents of the life-threatening diseases melioidosis and glanders,... (Review)
Review
: Two important pathogenic species within the genus , namely () and (), are the causative agents of the life-threatening diseases melioidosis and glanders, respectively. Due to their high mortality rate and potential for aerosolization, they have gained interest as potential biothreat agents and are classified as Tier 1 Select Agents.: The manuscript provides an overview of the literature covering the efforts taken in the last 10 years to develop new therapeutics measures against both and , with attention on novel therapeutic agents.: As a result of the complicated antibiotic regimens necessary to treat these infections, development of novel therapeutics is needed to treat both diseases. In recent years, the understanding of the pathogenesis of has improved significantly and so have the efforts to develop novel therapeutic agents with high efficacy, either alone, or in combination with conventional antibiotics.
Topics: Animals; Biological Products; Burkholderia mallei; Burkholderia pseudomallei; Glanders; Humans; Melioidosis
PubMed: 31590578
DOI: 10.1080/14712598.2019.1677602 -
Annals of Clinical Microbiology and... Feb 2019Bacteria belonging to the Burkholderia cepacia complex (Bcc) are among the most important pathogens isolated from cystic fibrosis (CF) patients and in hospital acquired... (Review)
Review
Bacteria belonging to the Burkholderia cepacia complex (Bcc) are among the most important pathogens isolated from cystic fibrosis (CF) patients and in hospital acquired infections (HAI). Accurate identification of Bcc is questionable by conventional biochemical methods. Clonal typing of Burkholderia is also limited due to the problem with identification. Phenotypic identification methods such as VITEK2, protein signature identification methods like VITEK MS, Bruker Biotyper, and molecular targets such as 16S rRNA, recA, hisA and rpsU were reported with varying level of discrimination to identify Bcc. rpsU and/or 16S rRNA sequencing, VITEK2, VITEK MS and Bruker Biotyper could discriminate between Burkholderia spp. and non-Burkholderia spp. Whereas, Bcc complex level identification can be given by VITEK MS, Bruker Biotyper, and 16S rRNA/rpsU/recA/hisA sequencing. For species level identification within Bcc hisA or recA sequencing are reliable. Identification of Bcc is indispensable in CF patients and HAI to ensure appropriate antimicrobial therapy.
Topics: Bacterial Proteins; Bacterial Typing Techniques; Burkholderia Infections; Burkholderia cepacia complex; Cross Infection; Cystic Fibrosis; DNA, Bacterial; Humans; Molecular Typing; Phylogeny; RNA, Ribosomal, 16S; Rec A Recombinases; Sequence Analysis, DNA; Whole Genome Sequencing
PubMed: 30717798
DOI: 10.1186/s12941-019-0306-0 -
The ISME Journal Sep 2018Disease-suppressive soils are ecosystems in which plants suffer less from root infections due to the activities of specific microbial consortia. The characteristics of...
Disease-suppressive soils are ecosystems in which plants suffer less from root infections due to the activities of specific microbial consortia. The characteristics of soils suppressive to specific fungal root pathogens are comparable to those of adaptive immunity in animals, as reported by Raaijmakers and Mazzola (Science 352:1392-3, 2016), but the mechanisms and microbial species involved in the soil suppressiveness are largely unknown. Previous taxonomic and metatranscriptome analyses of a soil suppressive to the fungal root pathogen Rhizoctonia solani revealed that members of the Burkholderiaceae family were more abundant and more active in suppressive than in non-suppressive soils. Here, isolation, phylogeny, and soil bioassays revealed a significant disease-suppressive activity for representative isolates of Burkholderia pyrrocinia, Paraburkholderia caledonica, P. graminis, P. hospita, and P. terricola. In vitro antifungal activity was only observed for P. graminis. Comparative genomics and metabolite profiling further showed that the antifungal activity of P. graminis PHS1 was associated with the production of sulfurous volatile compounds encoded by genes not found in the other four genera. Site-directed mutagenesis of two of these genes, encoding a dimethyl sulfoxide reductase and a cysteine desulfurase, resulted in a loss of antifungal activity both in vitro and in situ. These results indicate that specific members of the Burkholderiaceae family contribute to soil suppressiveness via the production of sulfurous volatile compounds.
Topics: Antibiosis; Burkholderiaceae; Carbon-Sulfur Lyases; Ecosystem; Fungi; Iron-Sulfur Proteins; Microbial Consortia; Oxidoreductases; Phylogeny; Plant Diseases; Soil; Soil Microbiology; Sulfur
PubMed: 29899517
DOI: 10.1038/s41396-018-0186-x